Abstract:Aim To study whether genetically predicted serum testosterone level is causally associated with systemic multisite atherosclerosis. Methods Based on two pooled databases of genome-wide association studies on testosterone and atherosclerosis in European populations from two separate foreign countries, the causal effect between testosterone and atherosclerosis was assessed using two-sample Mendelian randomization analysis with data on testosterone-associated genetic variants as instrumental variables (IV), and by using the inverse-variance weighted (IVW) method, MR-Egger regression, and weighted median estimation. Results IVW results showed that genetically predicted circulating testosterone levels were negatively associated with the risk of peripheral atherosclerosis (OR=0.3,5%CI:0.86~1.00, P＝0.01), and that elevated testosterone level may reduce the risk of developing peripheral atherosclerosis, while no evidence of a potential causal association was found with cerebral atherosclerosis, coronary atherosclerosis and other atherosclerosis type (P＞0.05). Conclusion The final analysis showed a causal relationship between genetically predicted testosterone level and the risk of developing peripheral atherosclerosis, and the role of testosterone therapy in the prevention and treatment of atherosclerosis deserves attention and further study.

Abstract:Aim To explore the potential causal association between galectin-1 (Gal-1) levels and atherosclerosis (As). Methods Single nucleotide polymorphisms (SNP) associated with Gal-1 served as instrument variables (IV), and the causal association between genetically predicted Gal-1 levels and As was analyzed by the two-sample Mendelian randomization (MR) method. Results Inverse variance weighted (IVW) results showed that genetically predicted Gal-1 levels were positively associated with risk of peripheral As and other As type (excluding cerebral artery, coronary artery, and peripheral artery) after Bonferroni adjustment (OR=1.6,5%CI:1.05～1.27, P＝0.002; OR=1.6,5%CI:1.12～1.20, P＝ 4.11E－17). There was no evidence supporting the causal association between Gal-1 and either coronary As or cerebral As (OR=1.2,5%CI:0.91～1.14, P＝0.765; OR=1.0,5%CI:0.94～1.29, P＝0.220); After Meta-analyzed the MR estimates of As outcomes at different sites, the results showed that genetically predicted Gal-1 levels were positively associated with As risk (OR=1.2,5%CI:1.06～1.19). ConclusionThe study suggests that genetically predicted Gal-1 level is causally associated with As risk, and Gal-1 is a potential target to prevent the occurrence of As.